Protocatechuic Acid Induces Angiogenesis through PI3K‐Akt‐eNOS‐VEGF Signalling Pathway

• Published in: Basic & clinical pharmacology & toxicology Vol. 113; no. 4; pp. 221 - 227
• Main Authors: Kang, Zechun, Zhu, Haibo, Jiang, Wanglin, Zhang, Shuping
• Format: Journal Article
• Language: English
• Published: Oxford Blackwell 01-10-2013; Wiley Subscription Services, Inc
• Subjects: Acids; Angiogenesis; Biological and medical sciences; Caspase 3 - genetics; Caspase 3 - metabolism; Cell Line; Cell Proliferation - drug effects; Cell Survival - drug effects; Chromones - pharmacology; Cinnamates - pharmacology; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Enzyme Inhibitors - pharmacology; Humans; Hydroxybenzoates - pharmacology; Medical sciences; Morpholines - pharmacology; Neovascularization, Physiologic - drug effects; Neovascularization, Physiologic - physiology; NG-Nitroarginine Methyl Ester - pharmacology; Nitric oxide; Nitric Oxide Synthase Type III - genetics; Nitric Oxide Synthase Type III - metabolism; Pharmacology. Drug treatments; Phosphatidylinositol 3-Kinases - genetics; Phosphatidylinositol 3-Kinases - metabolism; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; Signal Transduction; Up-Regulation; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor A - metabolism; Vascular Endothelial Growth Factor Receptor-1 - antagonists & inhibitors; Vascular Endothelial Growth Factor Receptor-1 - genetics; Vascular Endothelial Growth Factor Receptor-1 - metabolism; Angiogenesis; Signal transduction; Vascular endothelium growth factor; Acids; Signaling pathway; Enzyme; Transferases; Akt protein kinase; Oxidoreductases; Neovascularization; Nitric-oxide synthase; 1-Phosphatidylinositol 3-kinase
• ISSN: 1742-7835; 1742-7843
• DOI: 10.1111/bcpt.12094

In this study, we sought to elucidate whether protocatechuic acid contributes to induce angiogenesis as well as its mechanisms. To this end, we examined the role of protocatechuic acid on human brain microvascular endothelial cell line (HBMEC) proliferation, invasion and tube formation in in vitro. For the study of mechanisms involved, the phosphoinositide 3 kinase (PI3K)‐Akt inhibitor LY294002, the endothelial nitric oxide synthase (eNOS) inhibitor L‐NAME, vascular endothelial growth factor (VEGF), antagonist sFlt‐1 and VEGF receptor blocker SU‐1498 were used. Proliferation of HBMEC was tested by MTT. Scratch adhesion test was used to assess the ability of invasion. A Matrigel tube formation assay was performed to test capillary tube formation ability. PI3K‐Akt‐eNOS‐VEGF pathway activation in HBMEC was tested by Western blot. Our data suggested that protocatechuic acid induces angiogenesis in vitro by increasing proliferation, invasion and tube formation. VEGF expression was increasing by protocatechuic acid and counteracted by VEGF antagonist sFlt‐1, LY294002 and L‐NAME in HBMEC. Tube formation was increased by protocatechuic acid and counteracted by VEGF receptor blocker‐SU1498, LY294002 and L‐NAME. These data suggest that protocatechuic acid may be a candidate therapy for stroke recovery by promoting angiogenesis via a programmed PI3K/Akt/eNOS/VEGF signalling axis.